4 - Hypertension and Heart Failure Drugs Flashcards by Buneen Ayub

What are the effects of hypertension and how is bp regulated?

Increases arterial wall thickness by remodelling and hypertrophy. Stiffens the walls so they are less compliant
Organ damage from lack of blood flow
Regulated by RAAS, autonomic NS, bradykinin, NO and natriuretic peptides

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What are the values that define hypertension and what are some of the causes?

>140/90

primary, secondary (conn’s, diabetes), isolated diastolic/systolic, white coat

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What are target blood pressures (clinically and ambulatory) for different groups of people?

<140/90 if less than 80 inc type II diabetes
<150/90 if greater than 80
<135/85 if type I diabetic

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What is best practice when diagnosing hypertension?

Sitting relaxed and arm supported
Both arms should be within 15mm/Hg of each other, if not then repeat. Take highest reading
Measure over a period of time including ambulatory and hoe machines
CVD and organ damage should be assessed whilst waiting for hypertension confirmation

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What are the stages of hypertension?

Resistant hypertension at stage 3
Emergency if >180/20 and clinical signs

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What is prehypertension and how can progression of this be limited

>120/80 but less then 140/90

Promote regular exercise
Healthy balanced diet
Reduce stress and increase relaxation
Limit alcohol and caffiene intake
Smoking cessation
Reduce salt in diet

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In general what are some classes of drugs that are used to treat primary hypertension?

ACE inhibitors
ARBs
Calcium channel blockers
Diuretics
Alpha and Beta blockers

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What is the mechanism of action of ACEi’s to treat hypertension?

Competitive inhibitors of Angiotensin Converting Enzyme:

Reduce formation of angiotensin II
Arteriole vasodilation
Reduce circulating aldosterone so less ADH
Build up of bradykinin which is a vasodilator as makes NO, good for low renin hypertensives

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What are some examples of ACEi’s?

Ramipril
Lisinopril

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What are some side effects of ACEi’s?

Side effects:

- Dry cough*
Hypotension
- Hyperkalaemia* as loss of aldosterone
Renal failure especially due to renal artery stenosis as efferent arteriole needs to constrict
- Angiooedema* due to BK, especially black population

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What are some contraindications of using ACEi’s?

Pregnancy (along with ARBs, can cause CVS and CNS defects and growth restriction and oligohydraminos)
Hyperkalaemia

- NSAIDs, K+ raising drugs, antihypertensives

AKD
Breastfeeding
Renal artery stenosis

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What is the mechanism of action of ARBs?

- AngII mainly binds to AT1 receptor

- Inhibits vasoconstriction* better than ACEis as the AT1 receptor blocked so any AngII made from chymases can not work either
- Inhibits aldosterone stimulation*
Less effective in low renin hypertensives as no effect on bradykinin

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What are some examples of ARBs?

Candesartan
Losartan

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What are some side effects and contraindications of ARBs as antihypertensives?

Side effects:

No dry cough and angiooedema like ACEi
Renal failure
Hyperkalaemia

Contraindications:

AKD
Pregnancy and breast feeding
Renal artery stenosis
K+ raising drugs, NSAIDs, other antihypertensives

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What is the mechanism of action of calcium channel blockers?

- Bind to alpha1 subunit of L-type calcium channel (VOCC), reducing cellular calcium entry causing vasodilation, reducing preload on the heart

LTCC in vascuar smooth muscle, cardiomyocytes, SA and AV node. Different classes selective for different areas

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If a patient had hypertension with low renin levels, what class of drug would be best to prescribe them first?

- CCB as doesn’t target RAAS

ACEi as increases bradykinin

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What are the three main classes of CCBs and give some examples for each?

- Dihydropyridines: amlodipine (long half life), nifedipine (selective for cerebral vasculature so used for subarachnoid haemorraghe), nimodipine

- Benzothiazapines: Diltiazem

- Phenylakylamines: Verapamil

Where do each of the classes of CCBs work in the body?

- Dihydropyridines: 1st line CCB most commonly used for hypertension. Selective for peripheral vasculature but little ino/chronotropic effect

- Phenylalkyamines: mainly act on myocardium, depress the SA node and slows AV conduction so negative inotropy. Used for SVTS. Can worsen HF so don’t give to a hypertensive with heart failure

- Benzothiazapines: Sit in the middle, act on myocardium and vascular smooth muscle, can worsen heart failure

What are the side effects and contraindications of the use of dihydropyridines (good oral absorption) for hypertension?

Side effects:

Ankle swelling, flushing and headaches from vasodilation
Palpitations as compensatory tachycardia

Contraindications:

Unstable angina and severe aortic stenosis as the palpatations
Amlodipine and simvastatin as increased effect of statin
Other antihypertensives

What are the side effects and contraindications of the use of phenylalkylamines?

Mainly used to treat arrhythmias (SVTs) and angina not HTN

Side effects:

Constipation, bradycardia, heart block, cardiac failure

Contraindications:

Poor LV function
AV nodal conduction delay
B-blockers, other antihypertensives, other antiarrhytmic agents

What are the properties and adverse effects of Benzothiazepines e.g. diltiazem?

- Properties (same as phenylalkylamines): impedes calcium transport across the myocardial and vascular smooth muscle cell membrane, peripheral vasodilation, ↓ myocardial contractility

- Adverse effects: bradycardia, can worsen heart failure

What thiazide/thiazide-like diuretics are used to treat hypertension and what is their mechanism of action?

Reduce distal tubular sodium reabsorption by blocking NaCl channel

Initial blood volume decrease
Later, total peripheral resistance falls
RAAS compensates
Useful over CCBs in oedema

What are some examples of thiazides?

Bendroflumethiazide
Indapamide (thiazide like)

What are some side effects and contraindications associated with the use of thiazides in treating hypertension?

Side effects:

HypoK, hypoNa, hyperuricemia
Arrhythmia
Increased glucose
Increased cholesterol and triglycerides

Contraindications:

HypoK, HypoNa
Gout
NSAIDs, K+ lowering drugs

What are the steps recommended by NICE in treating primary hypertension?

**- ACD rule** with step 4 considering: - alpha/beta blocker/other diuretics - adherance of patient - referral to expert advice

Why are hypertensive type II diabetics treating with an ACEi first regardless of age?

- ACEi are antiproteinuric! Stops progression of diabetic nephropathy

What diuretics, other than thiazides, are added in step 4 of treating hypertension and what are the contraindications of this drug?

**- Spironolactone:** aldosterone receptor antagonist **- Contraindications:** - Hyper K - Addisons - K+ raising drugs, ACEis, ARBs

If a patient is at step 4 of treating hypertension but has hyperkaelamia, what other drug can be added to their regimen?

- NOT spironolactone as hyperkalaemic - Add alpha or beta blocker

What is a centrally acting drug?

- Lowers heart rate and reduces blood pressure by blocking sympathetic nervous system - e.g Labetalol in pregnancy or hypertensive emergency

What are the actions of betablockers and some examples?

- Reduce HR and CO - Inhibit renin release - Initially TPR increases later falls to normal - Labetalol, bisoprolol, metoprolol

What are some side-effects and contraindicaitons of the use of beta blockers?

**Side effects:** - Heart block - Lethargy - Impotence - Bronchospasms - Bradycardia - Impaired glucose tolerance **Contraindications:** - Asthma - Hepatic failure - Non-dihydropyridine CCBs as asystole

What are the mechanisms of actions of alpha receptor blockers? e.g **doxazosin**

**- Selective antagonism of a-1 adrenoreceptors** can be used for BPH and HTN - Antagonise contractile effects of NA on vascular smooth muscle - Reduce peripheral vascular resistance - Benign effect on plasma lipids / glucose

What are some side effects and contraindications of the use of alpha blockers?

**Side effects:** postural hypotension so dizziness, syncope, headche and fatigue, oedema **Contraindications:** postural hypertension or taking dihydropyridine CCBs

What are the causes of heart failure and how can non-pharmacological treatment help to alleviate symptoms like oedems, dyspnoea?

- Ischaemic heart disease - Hypertension - Valve disease - Reduce salt intake, exercise and stop smoking and drinking alcohol

In four steps, describe the clinical management of heart failure

- Diuretics - ACE inhibitor - ARB - β-blocker - Spironolactone Drugs are given to help sympoms, delay progression and reduce mortality

What drugs are given to a patient diagnosed with heart failure?

**- Furosemide** loop diuretic to relieve symptoms **- ACEi** (ramipril) and **Beta blocker** (bisoprolol) to reduce heart rate, b.p and therefore the work load and oxygen demand of the heart **- Spironolactone** if needed as refractory hyperaldosteronism may occur - Statins if heart failure due to MI

Why are older and black patients treated with CCBs rather than ACEi's for hypertension initially?

These populations have lower renin levels

What drug treatment would you consider at this stage?

Post MI bundle: **- Beta blocker** (be careful as asthmatic) - ACEi - High dose statin - Antiplatelet

What should your plan of action be for the following clinic blood pressures: - \<140/90 - 140/90 to 179/110 - 180/20 or more

What are some actions of ACEi's that lower blood pressure?

- Less vasoconstriction - Less sympathetic activity - Less aldosterone so less salt and water retention

Which diureic is an add on therapy in resistant hypertension?

**Spironolactone** if patient has normal K+ levels. Thiazide already added in three step approach

What are some drugs added in resistant hypertension, apart from a diuretic?

**Beta Blocker** (e.g bisoprolol): lowers renin levels, -ve chronotrope, decreases cardiac output **Alpha Blocker** (doxazosin): causes vasodilation reducing PVR